Milo supported Pompey and thus became pitted against Clodius, a reckless and disruptive politician who had allied himself with Julius Caesar. Milo organized gangs of mercenaries and gladiators and led them in clashes against the partisans of Clodius in Rome from 57 to 52 bc. As tribune of the plebs in 57, Milo actively promoted the recall of Cicero, whom Clodius had managed to have exiled. Milo tried unsuccessfully to prosecute Clodius and prevent his election to the aedileship, and Clodius, in turn, failed in an attempt to press charges against Milo. After serving as praetor in 55, Milo in 53 was a candidate for the consulship, while Clodius was seeking the praetorship. A confrontation between the two leaders at Bovillae ended with the murder of Clodius (January 52).

Milo’s guilt in the murder was clear. Pompey was made sole consul for 52 and passed a strict law against public violence (vis), under which charges were brought against Milo. He was impeached and prosecuted, his enemies using a variety of means to intimidate the judges and his supporters. Cicero broke down and was unable to deliver an effective defense at the trial; his extant oration Pro Milone is an expanded form of the unspoken defense. Milo retired into exile at Massilia (now Marseille, France). He joked that if Cicero had delivered the speech in his defense, he would never have been able to enjoy the fine mullets of Massilia. Milo was the only man barred from Julius Caesar’s general amnesty. Joining Marcus Caelius Rufus in 48 in an uprising against Caesar, Milo was killed near Thurii.